Triethylamine → (S)-N-[(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)(oxido)phenyl--sulfanylidene]-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)nicotinamide

HRID 607448Notes

Reaction equation

HRID 607448 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:29]=1)[C:7]([N:9]=[S@@:10]([CH2:18][CH2:19][CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8].[C:30]([C:32]1[CH:33]=[C:34]([NH:38][C:39]([C:41]2[O:42][CH:43]=[CH:44][C:45]=2[CH3:46])=[O:40])[CH:35]=[CH:36][CH:37]=1)#[CH:31].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Si:22]([O:21][CH2:20][CH2:19][CH2:18][S@:10](=[O:17])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[N:9][C:7](=[O:8])[C:6]1[CH:29]=[C:2]([C:31]#[C:30][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([NH:38][C:39]([C:41]3[O:42][CH:43]=[CH:44][C:45]=3[CH3:46])=[O:40])[CH:33]=2)[CH:3]=[N:4][CH:5]=1)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 51337833N-(3-ethynylphenyl)-3-methylfuran-2-carboxamideHCID 86629482(S)-5-bromo-N-[(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)(oxido)phenyl--sulfanylidene]nicotinamide

Product 1

HCID 86629484(S)-N-[(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)(oxido)phenyl--sulfanylidene]-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)nicotinamideYield 90%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To the solution of (S)-5-bromo-N-[(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)(oxido)phenyl--sulfanylidene]nicotinamide (1.9 g, 3.82 mmol) in anhydrous DMF (19 mL) under nitrogen atmosphere was added sequentially 3-methyl-furan-2-carboxylic acid (3-ethynyl-phenyl)-amide (1.72 g), triethylamine (2.13 mL), bis(triphenylphosphine)palladium(II) dichloride (268 mg), and triphenylphosphine (25 mg). The reaction system was placed under a N2—H2 (1:1) atmosphere and CuI (145 mg) was added in one portion. After the reaction mixture was stirred and heated at 60° C. for 1.5 hours, it was poured into saturated aqueous NaHCO3. The aqueous was extracted with EtOAc (1×), which was subsequently washed with aqueous NaHCO3 (1×), brine (1×), and dried (anhydrous Na2SO4). The organic layer was decanted, evaporated and wrapped with silica gel. Two times column chromatography (EtOAc-Hex:from 1:4 to 1:2; and MeOH—CH2Cl2: 1:100) gave the title compound as yellow foam (2.2 g, 90%).

Workup

  1. extractionThe aqueous was extracted with EtOAc (1×), which
  2. washwas subsequently washed with aqueous NaHCO3 (1×), brine (1×)
  3. dry with materialdried (anhydrous Na2SO4)
  4. customThe organic layer was decanted
  5. customevaporated

Sources & evidence

ORD record
ord-aeb3a57f06784cc797d49b1cfca6f590
Source dataset
uspto-grants-2011_03
Patent number
US07915443B2

Reaction notes

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